Efficacy and Safety of add-on Apremilast Versus add-on Methotrexate in Patients With Oral Lichen Planus

All India Institute of Medical Sciences, Bhubaneswar

Status and phase: Not yet enrolling; Phase 4

Conditions: Oral Lichen Planus

Treatments: Drug: Prednisolone; Drug: Apremilast; Drug: Methotrexate

Study type: Interventional

Funder types: Other

Identifiers

NCT06260904

AIIMS BBSR/PGThesis/23-24/112

Details and patient eligibility

About

Lichen planus is an inflammatory disorder of unknown aetiology affecting the stratified squamous epithelia, with an estimated global prevalence of 0.22 to 0.5 %. Oral mucosa (Oral Lichen Planus; OLP) is the most commonly affected region. Corticosteroids are the primary treatment of choice. A prolonged treatment with steroids is required for clinical improvement, which increases the chances of long-term adverse effects. So, there is a need for newer, effective treatment modalities, such as retinoids, methotrexate, Janus kinase inhibitors, PDE4 inhibitors, etc.

Of these, methotrexate is a dihydrofolate reductase inhibitor that inhibits the replication and function of T and B lymphocytes. It has shown a good response to OLP (around 83%) in a study by Lajevardi et al. and can be considered a treatment option in patients with moderate to severe OLP. Apremilast is a drug with a novel immunomodulatory mechanism of action. It inhibits phosphodiesterase type IV, which increases levels of cyclic adenosine monophosphate (cAMP), thus activating protein kinase A and inhibiting various inflammatory mediators. Based on a pilot study by Paul et al., apremilast is associated with clinical improvement in lichen planus.

Among the various treatment options, there is a lack of head-on trials. Methotrexate is an immunosuppressant with various systemic adverse effects and requires close monitoring. Whereas apremilast is a non-immunosuppressive drug with a better safety profile, it does not show such adverse effects. These drugs can be used as an add-on to low-dose steroids in view of reducing the adverse effects associated with steroid therapy. To the best of our knowledge, there is no randomized controlled trial comparing these two drugs to date. Hence, the present study has been planned to evaluate the safety and efficacy of methotrexate versus apremilast as an add-on to the standard steroid therapy in OLP patients.

Enrollment: 64 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients aged ≥18 of either sex with the clinical diagnosis of oral lichen planus.
• Patients with a PGA score of ≥3 (moderate and severe oral LP).
• Patient not responding to topical or intralesional corticosteroid.
• Patients who are willing to give informed written consent.

Exclusion criteria

• Treatment with a systemic corticosteroid within the last 4 weeks.
• Patients on any immunosuppressive agents such as azathioprine, cyclosporine and others within one month of recruitment.
• Patients with clinical history and any lesion distribution suspicious of a lichenoid drug eruption and patients with other skin diseases.
• Past or current history of any malignancy including moderate to severe dysplasia of the oral mucosa on oral biopsy.
• Severe active infection, including active tuberculosis, hepatitis B or C infection
• Patients with cytopenia (Hb <9g/dl, leukocyte count <4000/mm3, platelet count <100,000/mm3)
• Patient with history of alcohol abuse.
• Decreased liver or renal function (creatinine > 2.0mg/dl, total bilirubin > 2.5 mg/dl).
• Severe acute infection, uncontrolled diabetes mellitus, untreated glaucoma, congenital or acquired immunodeficiency, active gastroduodenal ulcer, severe osteoporosis, severe cardiac disease (NYHA grade IV), MI in the last four weeks, severe schizophrenia or depression.
• Patient with a history of hypersensitivity to Methotrexate or Apremilast.
• Pregnancy and lactation, women of childbearing age without effective contraception.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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64 participants in 2 patient groups

Prednisolone and Methotrexate (Control Arm)

Active Comparator group

Description:

prednisolone 0.75mg/kg/day (a maximum dose of 30mg at baseline) and Methotrexate 15 mg weekly for 12 weeks.

Treatment:

Drug: Methotrexate

Drug: Prednisolone

Prednisolone and Apremilast (Test Arm)

Experimental group

Description:

prednisolone 0.75mg/kg/day (a maximum dose of 30mg at baseline) and Apremilast 30 mg twice daily for 12 weeks.

Treatment:

Drug: Apremilast

Drug: Prednisolone